POS0460 IMPACT OF MAINTENANCE THERAPY WITH LOW-DOSE GLUCOCORTICOIDS IN PATIENTS UNDERGOING BIOLOGICAL AND TARGETED SYNTHETIC DMARDS FOR RHEUMATOID ARTHRITIS
Authors: A. Giollo, M. Zen, M. Salvato, F. Frizzera, K. Botsios, R. Ramonda, A. Doria
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> The benefit and harms of low-dose glucocorticoid (GC) therapy for established rheumatoid arthritis (RA) in combination with biological and targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs) are uncertain. <h3>Objectives</h3> We investigated the effect of b/tsDMARDs on concomitant GC therapy among people with RA and the impact of low-dose GC therapy on disease activity and comorbidities. <h3>Methods</h3> This was an observational, monocentric, prospective study. We enrolled all RA patients who started their first b/tsDMARD between 2015 and 2020, excluding those with overlapped connective tissue diseases. The primary outcome was the odds ratio (OR) of persistent GC discontinuation at month 36 (M36), as assessed through multivariable logistic regression. We defined persistent GC discontinuation if GC therapy was not prescribed for ≥2 consecutive visits after 24 months. Secondary outcomes were the marginal means of prednisone daily dose and disease activity score in 28 joints (DAS28) with C-reactive protein (CRP) over three years estimated through repeated-measures analysis of covariance. Analyses were adjusted for age, sex, disease duration, seropositivity, baseline DAS28 or GC dose. The impact of low-dose GC therapy on comorbidities and disease activity was also evaluated. <h3>Results</h3> This inception cohort comprised 371 RA patients initiating their first b/tsDMARD: tumor necrosis factor inhibitors (n=298; 80.3%), abatacept (n=47; 12.7%), tocilizumab (n=11, 3.0%), rituximab (n=9; 2.4%), Janus kinase inhibitors (n=9; 1.6%). b/tsDMARDs were combined with low-dose GC therapy in 65% of patients at baseline, decreasing to 42% at M36. After starting b/tsDMARDs, the median (10th-90th percentile) dose of prednisone decreased from 5 (2-10) at baseline to 2.5 (0-5) mg daily at M36. The most decrease in prednisone dose occurred within the first six months of b/tsDMARD therapy. Persistent GC discontinuation was achieved in 23% of patients during follow-up, with a significantly higher discontinuation rate (34%) and a trend for lower exposure to GC therapy after M24 in patients diagnosed in the last decade compared to older cohorts (<b>Figure 1A</b>). Patients who discontinued GC therapy persistently were significantly younger (52 vs 59 years), had shorter disease duration (9 vs 13 years), more swollen joints (6 vs 4) and greater patient global assessment (65 vs 55 mm), and received higher doses of methotrexate (14 vs 12 mg/w). After accounting for confounders, patients who discontinued GC therapy persistently did not show worse disease control over time (<b>Figure 1B</b>) whilst developed less cardiovascular disease, especially hypertension (9% vs 19%, p=0.023) and coronary artery disease (0% vs 4.6%, p=0.044). Changing the molecular targets of b/tsDMARDs did not yield higher odds of persistent GC therapy discontinuation than keeping the initial drug class; in contrast, GC persistent discontinuation was less likely in older patients with longer disease duration (Table 1). Patients refractory to more than three b/tsDMARDs classes had numerically higher disease activity and received more prednisone during follow-up (<b>Figures 1C and D</b>). <h3>Conclusion</h3> Low-dose GC therapy for RA persists in the majority of patients despite intensive use of b/tsDMARDs, yet is associated with cardiovascular morbidity and negligible effect on disease activity. This study also highlights a trend towards less reliance on GC therapy over the past 30 years. <h3>REFERENCES:</h3> NIL. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> Alessandro Giollo Speakers bureau: Galapagos, Eli Lilly, Consultant of: Galapagos, Novartis, Sandoz, Margherita Zen: None declared, Mariangela Salvato: None declared, Francesca Frizzera: None declared, Konstantinos Botsios: None declared, Roberta Ramonda: None declared, Andrea Doria Consultant of: GSK, Astra Zeneca, UCB.